Bai Long, Su Jiacan
Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
MedEng-X Institutes, Shanghai University, Shanghai, 200444, China.
Bioact Mater. 2025 Dec 22;59:45-68. doi: 10.1016/j.bioactmat.2025.12.030. eCollection 2026 May.
Organoid platforms have reshaped in vitro human biology yet remain constrained by batch variability, sparse longitudinal readouts and barriers to scale. This review introduces Artificial Intelligence Virtual Organoids (AIVOs), also termed silicon organoids: organoid-scale digital twins instantiated in the computational space, with virtual cells-and, where appropriate, virtual organoids-serving as the minimal executable units. AIVOs fuse multimodal and longitudinal measurements into universal state representations and use virtual instruments constrained by biophysical priors to emulate assays and perturbations, while hybrid mechanistic modules (agent-based, continuum, finite-element) capture cell-cell, cell-matrix and transport dynamics. The article defines conceptual boundaries, formalizes a data-model-interaction architecture and construction strategies, and synthesizes evaluation and standardization practices. Applications span drug screening and dosing design, disease subtyping and resistance mapping, integration with organoid-on-chip systems and clinical decision support. Principal challenges include the acquisition and harmonization of high-quality longitudinal data, scalable computation and model reduction, interpretability and causal reasoning, and governance addressing privacy, safety and fairness. Virtual organoids ultimately provide a silicon-grounded, transparent and reproducible bridge between physical organoids and clinical practice, enabling high-throughput in silico experiments and active experiment design without added experimental burden and accelerating precise therapy, mechanism discovery and regulatory translation.
类器官平台重塑了体外人类生物学,但仍受批次变异性、稀疏的纵向读数和规模障碍的限制。本综述介绍了人工智能虚拟类器官(AIVOs),也称为硅基类器官:在计算空间中实例化的类器官规模的数字孪生体,其中虚拟细胞以及在适当情况下的虚拟类器官作为最小可执行单元。AIVOs将多模态和纵向测量融合到通用状态表示中,并使用受生物物理先验约束的虚拟仪器来模拟分析和扰动,而混合机制模块(基于代理、连续体、有限元)则捕捉细胞间、细胞与基质以及运输动力学。本文定义了概念边界,形式化了数据-模型-交互架构和构建策略,并综合了评估和标准化实践。其应用涵盖药物筛选和给药设计、疾病亚型分类和耐药性图谱绘制、与芯片上类器官系统的集成以及临床决策支持。主要挑战包括高质量纵向数据的获取与协调、可扩展计算和模型简化、可解释性和因果推理,以及涉及隐私、安全和公平性的治理。虚拟类器官最终在物理类器官和临床实践之间提供了一个基于硅的、透明且可重复的桥梁,实现高通量的计算机模拟实验和主动实验设计,而无需增加实验负担,并加速精准治疗以及机制发现和监管转化。